CHAPTER 8 DRUG INTERACTIONS AND OVER-THE-COUNTER DRUGS DRUG INTERACTIONS a drug interaction is defined as an altered or modified action or effect

t of a drug as a result of interaction with one or more other drugs. o Should not be confused with adverse drug reaction or incompatibility Adverse drug reaction = undesirable drug effect that ranges from mild untoward effects to severe toxic effects, hypersensitivity or anaphylaxis. Drug incompatibility = chemical or physical reaction that occurs among two or more drugs in vitrowithin a syringe, IV bag or any other artificial environment

Pharmacokinetic Interactions changes that occur in the absorption, distribution and metabolism or biotransformation and excretion of one or more drugs

Absorption when a person takes two drugs at the same time the rate of absorption of one or both drugs can change o one drug can bloc, decrease or increase the absorption rate of another drug: by decreasing or increasing gastric emptying time by changing the gastric pH by forming drug complexes increasing the speed of gastric emptying may lead to an increase in gastric and intestinal motility and cause decreases in absorption most drugs are absorbed in the small intestine, exceptions are barbiturates, salicylates and theophylline o narcotics and anticholinergic drugs decrease gastric emptying time and gastrointestinal mobilityincrease in absorption drugs that undergo gastric absorptionthe amount or extent of absorption increases the longer the drug remains in the stomach weakly acidic drugs such as aspirin are more rapidly absorbed when gastric pH is decreased o drugs that increase pH of gastric juices decrease absorption of weak-acid drugs Certain cholesterol-lowering drugs form complexes with drugs o Drugs become less solubleless drug absorption Alteration of bacteria normally found in the GI tract may impact the pharmacokinetics of a medication o Intestinal microflora have the ability to metabolize digoxindecreases the bioavailability o Gut bacteria are necessary to hydrolyze estrogen conjugates into free estrogens so that they may be optimally absorbed to exert their contraceptive effect Concurrent antibiotic administration may alter these bacteriaprevents optimal absorption

Distribution drugs distribution to tissues can be affected by its binding to plasma/serum protein o drugs unbound to protein are free active agents and can enter body tissues o two drugs that are highly protein-bound and administered simultaneously can result in drug displacements. o Factors that influence displacement: Drug concentration in the blood Protein-binding power of the drugs Volume distribution (Vd) Two drugs that are highly bound to protein or albumin will compete for binding sites in the plasma

Result is a decrease in protein binding of one or both drugs; therefore more free drug circulates in the plasma and is available for drug actiondrug toxicity

Metabolism or Biotransformation drug interactions of metabolism occur with the induction or inhibition of the hepatic microsomal system o drug can increase metabolism of another drug by stimulating liver enzymes enzymes produce a cascade effect in drug functiondrugs promote induction of enzymes are called enzyme inducers increased metabolism promotes drug elimination and decreases plasma concentration of the drug decrease in drug action sometimes liver enzymes convert drugs to active or passive metabolites; may be excreted or may produce an active pharmacologic response cigarette smoking increases hepatic enzyme activity and can increase theophylline clearance some drugs are enzyme inhibitors use of tobacco and alcohol may have variable effects on biotransformation o polycyclic aromatic hydrocarbons found in cigarette induce production of the specific family of enzymes responsible for the theophylline metabolism chronic cigarette smoking leads to an increase in hepatic enzyme activity and can increase theophylline clearance natural and herbal products may also have an impact on metabolism

Excretion most drugs are filtered through the glomeruli and excreted in the urine o with some drugs, excretion occurs in the bile which passes into the intestinal tract o drugs can increase or decrease renal excretion or have an effect on the excretion of other drugs o drugs that decrease cardiac output decrease blood flow to the kidneys, decrease the glomerular filtration ratecan also decrease or delay drug excretion diuretics promote water and sodium excretion from the renal tubules o decrease reabsorption of water, sodium, potassium renal loss of potassium which may lead to a condition known as hypokalemia can enhance the action of digoxin and digitalis toxicity two or more drugs that undergo the same route of excretion may compete with one another for elimination from the body changing urine pH affects drug excretion o antacid sodium bicarbonate causes urine to be alkalinepromotes the excretion of drugs such as quinidine that are weak bases clients who have decreased renal or hepatic function, usually an increase in free drug concentration there is usually an increase in free drug concentration. o Essential to closely monitor such a client for drug toxicity

Pharmacodynamic Interactions those that result in additive, synergistic or antagonistic drug effects

Additive Drug Effect additive drug effect = two drugs with similar action are administered o effects can be desirable or undesirable

Synergistic Drug Effect or Potentiation

when two or more drugs are given together, one can potentiate or have a synergistic effect on the other o clinical effect is substantially greater than the combined effect of the two

Antagonistic Drug Effect two drugs that have opposite effects are administered together, each drug cancels the effect of the other o actions of both drugs are nullified sometimes antagonistic effect is desirable

DRUG-FOOD INTERACTIONS -